A New Sequence of the Barley Genome Could Open the Taps on Better Beer

The genome of barley—the grain that’s the soul of beer and whiskey—is weird. The commodity crop has just seven pairs of chromosomes (compared to your 23, assuming you are a human being) but twice the size of your genome overall, with the vast majority of the sequences repeating themselves.

And you care because (making the same assumption again) you care about beer and whiskey, even just in the abstract. Short version, barley is very good at making an enzyme that turns starch—in barley, but also in corn or rice or whatever—into the sugar that yeast eats and turns into alcohol. So geneticists and agronomists would love to have some options for getting under barley’s hood and souping it up.

They got a start in 2012, when the International Barley Genome Sequencing Consortium published the first physical map of the barley genome. This week, that work got a serious push forward—one that could turn out to be as significant the moment six millennia ago when farmers in the Fertile Crescent started trying to breed improvements into the tasty beer-making grass growing outside their huts. Lots of the same researchers from that 2012 paper are back with new work, published in the journal Nature: a much higher-resolution sequence for barley. To barley breeders, it’s a green light to start tinkering in earnest.

What Better Barley Would Be

Like other grains, barley stores energy not as simple sugars but as a polymer of sugars, otherwise known as starch. But barley has a quality those other grains don’t. It’s possible to induce it to make an enzyme, alpha-amylase, that breaks starch into ready-to-use sugar. The process of coaxing that enzyme out is called malting, and malted barley is what you use to make beer—even if you’re adding in other grains like corn or rice, as major American brewers do. The enzyme in the malt turns those grains’ starches into sugar, too, and that’s what yeast converts to alcohol. Yay!

In 2012, when that initial barley genome paper came out, three-quarters of the worldwide barley crop went to animal feed. Today, 65 percent of the US barley crop is for malting—for eventual purchase by brewers. (About 2 percent goes to distillers, who make whiskey basically by distilling beer. I know that’s a gross oversimplification, I wrote a book about it, don’t @ me.) So yes, breeding programs around the world are on the constant hunt for barley strains that’ll better meet the needs of brewers and distillers and drinkers. That’s what the new, more complete sequence is for. “First of all it is a tool that will facilitate and improve the strategies in classical breeding,” says Nils Stein, a geneticist at the Leibniz Institute of Plant Genetics and Crop Plant Research in Germany who was the lead author on the new paper. “Then, of course, this information is also the basis for designing strategies for modern breeding technologies like genome editing.”

So what kind of traits make a better barley? Resistance to disease, sure, and the ability to grow in hotter climates. But farmers have other priorities, too. “One is lodging resistance, and that’s partly height and partly straw strength. We want that barley to stand all the way through harvest,” says Gary Hanning, director of global barley research for Anheuser-Busch InBev, the biggest brewing company in the world—Budweiser, Corona, Stella Artois, Hoegaarden, Michelob, and Modelo are all in its portfolio. “Can we get barley harvested earlier than wheat? If a grower’s barley comes off at the same time his wheat does, and he has 10 times as much wheat, he’s probably going to harvest wheat.”

And, maybe most critically, it has to make better malt. “That basically goes down to what we call modification rates,” Hanning says. That’s modifying starch into sugar. His lab and people working with the American Malting Barley Association will grow up new varieties and measure soluble proteins, levels of beta-glucan, free amino nitrogen, enzymes … all qualities that determine how well a barley will turn into a beer. Not because growers love beer, mind you. Because it’s the only stuff that makes money. Feed barley doesn’t cover its costs; malt barley makes a profit. “If we’re contracting with growers, we want them to successfully produce malting barley that meets our specifications,” says Mike Davis, president of the American Malting Barley Association. “We have to mitigate risk and we try to keep barley competitive with other crops. Growers are businesspeople and they have a lot of options. They’re going to grow what gives them a return.”

Brewing as a business has its ups and downs, but 2.1 new brewing startups open every day (net) in the US—many of them looking for all-malt beers or specialty malting. So the business needs good malt. “First it was the growth of the craft brewing industry, and now we have growth in the craft malting industry,” Davis says. “Have you heard the term ‘locavore?’”

As a journalist who sometimes covers food and booze in San Francisco, I am required to have a tattoo of that word. So yes.

Building Better Barley

The new genome may actually be able to help with some of those demands. It covers 5.2 billion base pairs, 98 percent of the barley genome, including the repetitive sequences that make up 80 percent of the overall code. “We know all the genes. We know the linear order to them. We know the genomic context,” Stein says. That’s the information a breeder needs to correlate genotype with phenotype—genes with the traits they code for—and start to make tweaks.

Even cooler, Stein’s international team has already learned more about malting. In the reference strain they sequenced, an old Minnesota malting variety called Morex, the gene for alpha-amylase repeats multiple times, with slight variations. “That really adds to our knowledge on how to improve the levels of that,” Hanning says. “With multiple copies we can choose which ones we want to increase.” Simple edits might increase production of alpha-amylase, for example, improving modification rates. That could speed up malting time, or allow for less energy input. Or not! But it gives barley researchers something to test.

Looking at an assortment of other strains, Stein’s group also learned that huge chunks of genome have what he describes as a “reduced level of diversity.” Which is to say, no matter what strain of barley you’re looking at, big pieces of its genetics are the same as any other strain. No one knows why. “Has selection already brought into combination the best alleles for modern varieties?” Stein says. “Or is this just something that happened because people always selected the same, and there was a domestication bottleneck?” Whether domestication perfected or broke these regions, they’ll make excellent targets for improvement.

The question is how to improve them. Unlike, say, corn, researchers haven’t genetically modified barley. That’s not because the locavores would whine about it. It’s because of economics. The world grew over a billion metric tons of corn in the past year and just 147 million metric tons of barley. “It costs about $140 million to commercialize a GM trait,” Davis says. “So because of the small market, none of the biotech seed companies are pursuing biotech barley.” Even if they did, it’d be a decade before one came to market.

“That’s why I’m excited about this genomic breakthrough,” Davis says. “What we can do is track genes, and then use both traditional breeding and methods of biotechnology to move along the development of malting barley varieties.” Though it’s still early days for the gene editing technology Crispr/Cas9 (and it has some IP issues to work out), it’s famously easier to deploy than older methods, and doesn’t require the industrial infrastructure that, say, introducing new genes via an agrobacterium would. Oh, and using Crispr to knock out genes doesn’t seem to have the same regulatory issues that jamming in a whole new gene from some other organism does.

As with most genomic work, the new barley map still has room for more detail. Stein’s institution has a seed bank with 20,000 different kinds of barley. “We’re in the process of genotyping all these 20,000 accessions,” he says. Continuing to hammer away at a problem? That’s all too human, too.

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